Principal Research Interests

Natural Product Chemistry and Metabolomics

Functional Analysis and Inhibition of Enzymes in Sterol Biosynthesis Pathways

Mechanistic Enzymology of Sterol Catalysts

The main focus of Professor Nes' research has been to establish the origin, biosynthesis
and function of sterols in a range of organisms by unearthing the molecular libraries
(genome-metabolome congruence) associated with the phyla-specific reaction sequences
that regulate sterol patterning in nature. Particular emphasis is directed at the
structure and mechanism of sterol catalysts and the characterization of intracellular
metabolite and enzyme specificities involved in sterol production and processing.
We have determined the structure of a panoply of naturally occurring isoprenoids and
other lipids in stereochemical detail using 1H/13C-NMR/X-ray crystallography and tracked
2H and 13C-labeled intermediates to final products using sensitive labeling techniques.
In parallel studies, we have cloned and demonstrated the mechanism and physiological
abundance of crucial sterol catalysts in parasites as well as genetically modified
sterol biosynthesis in crops.Our research program also involves fruitful collaborations
involving several laboratories, including the Waterman/Lepesheva (Nashville, TN),
Nguyen (Columbia, MO), Snell (Dallas, TX) and Kelly (Swansea, Wales) laboratories
to rationally design and prepare substrate-based inhibitors targeted at 24-alkyl sterol
biosynthesis and to examine the factors regulating carbon flux and sterol homeostasis.
These studies have led to chemotherapeutic leads to prevent disease by opportunistic
parasites dependent on an intact ergosterol pathway and afforded success in engineering
transgenic plants with modified sterol seed compositions to benefit human health.